DPP-4 Inhibitors Tied to Blistering Skin Condition - MedPage Today

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Among people with type 2 diabetes, new treatment with a dipeptidyl peptidase 4 (DPP-4) inhibitor was linked with higher risk of a rare blistering skin condition, researchers reported.

Compared with new initiators of a second-generation sulfonylurea, those who started treatment with a DPP-4 inhibitor had a 42% higher risk of developing bullous pemphigoid during the course of a year (hazard ratio 1.42, 95% CI 1.17-1.72), according to Hemin Lee, MD, MPH, of Brigham and Women's Hospital in Boston, and colleagues.

This elevated risk equated to a bullous pemphigoid incidence rate of 0.42 among DPP-4 inhibitor users versus 0.31 for sulfonylurea users per 1,000 person-years, they wrote in JAMA Dermatology.

However, certain clinical factors such as age, race, and which agent in the class of DPP-4 inhibitors all played roles in modifying this risk.

Specifically, patients age 65 and older on a DPP-4 inhibitor saw a 62% higher risk for developing bullous pemphigoid compared with like-age sulfonylurea users (incidence rates 0.79 vs 0.49, HR 1.62 95% CI 1.32-1.99). Also, this risk was even more pronounced in white patients, who saw a 70% increased risk for this skin condition while taking a DPP-4 inhibitor versus sulfonylurea versus non-white patients (0.93 vs 0.54, HR 1.70 95% CI 1.30-2.24).

Also, patients who were specifically treated with the DPP-4 inhibitor linagliptin (Tradjenta) had a 68% increased risk for bullous pemphigoid versus those on a second-generation sulfonylurea (1.20 vs 0.55, HR 1.68, 95% CI 1.16-2.43).

These higher risks for bullous pemphigoid were similarly elevated for both men and women.

Despite these findings, Lee explained to MedPage Today that the absolute risk for developing bullous pemphigoid was overall low, and not all cases were linked to serious morbidity or mortality. "And clinically, we see DPP-4 inhibitor induced bullous pemphigoid cases remitting after discontinuing the culprit drug," she stated.

Lee added that she and her colleagues weren't necessarily surprised to see this increased risk DPP-4 inhibitor initiators versus sulfonylurea initiators, as its consistent with prior findings. Previous research has also "frequently" linked vildagliptin (Galvus) to a higher risk for bullous pemphigoid, although this agent isn't currently available in the U.S.

But what was new were the elevated risks observed in older adults, linagliptin users, and especially white race, which could serve as a topic for future studies to explore further, she suggested.

"Nevertheless, clinicians should increase their awareness on the potential onset of bullous disease in patients initiating DPP-4 inhibitors -- especially those with older age, white race, and initiating linagliptin," Lee noted. But ultimately clinicians shouldn't shy away from prescribing DPP-4 inhibitors for otherwise good candidates for the therapy, according to the authors.

The cohort study included a total of 1,664,880 U.S. patients from two large commercial insurance claim databases and Medicare data. All individuals had type 2 diabetes and were new users of either a DPP-4 inhibitor -- which include saxagliptin (Onglyza), sitagliptin (Januvia), linagliptin (Tradjenta), or alogliptin (Nesina) -- or a second-generation sulfonylurea, such as glyburide (Glynase), glimepiride (Amaryl), and glipizide (Glucotrol and Glucotrol XL).

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  Kristen Monaco is a staff writer, focusing on endocrinology, psychiatry, and dermatology news. Based out of the New York City office, she’s worked at the company for nearly five years.

Disclosures

The study was supported by the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, and by the National Institute on Aging.

Lee disclosed no relevant relationships with industry. A co-author disclosed support from Boehringer Ingelheim through Brigham and Women's Hospital.

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